Immunotherapy recruits and activates T cells that recognize tumor-specific antigens. Success for this approach in pancreatic cancer has been limited to date, potentially due to the amount of disease burden and tumor immune escape, Dr. Miksad pointed out.

Questions Remain

“Researchers at Johns Hopkins have developed a heterologous prime boost approach in an attempt to improve immunotherapy for pancreatic cancer,” she noted. “The phase II survival results are encouraging, and the sequential administration of CRS-207 after cyclophosphamide and GVAX appears to be tolerable.”

Dr. Miksad commented, “it makes sense from an immune therapy point of view and for the study design” to assess patients after three doses of immune therapy (three doses of cyclophosphamide and GVAX or two doses of cyclophosphamide and GVAX followed by one dose of CRS-207), since “it takes time to develop an appropriate immune response.” But this means “we must still contend with the fact that 30% of patients did not make it to the point of the third dose and, therefore, we were excluded from the per-protocol analysis.” Fortunately, analysis of all subjects who received one dose also demonstrated a benefit for the combination arm, although the survival improvement was smaller.

She also questioned the generalizability of the study, which included a “highly selected” population: 40% had undergone surgical resection and 80% received chemotherapy for metastatic disease. Most importantly, the standard of care for first-line treatment of advanced pancreatic cancer has changed since this study was conducted. “The standard of care for first-line treatment of advanced pancreatic cancer has changed since the study was conducted. Will these findings hold for patients exposed to modern combination regimens?” she wondered.

“Immunotherapy may offer a treatment alternative for pancreatic cancer, but it’s resource-intensive. We eagerly await the results of the three-arm trial,” she said. ■